omacor and Inflammation

Fish oil-derived n-3 PUFA may improve cardiometabolic health through modulation of innate immunity. However, findings in clinical studies are conflicting. We hypothesized that n-3 PUFA supplementation would dose-dependently reduce the systemic inflammatory response to experimental endotoxemia in healthy humans.. The Fenofibrate and omega-3 Fatty Acid Modulation of Endotoxemia (FFAME) study was an 8-wk randomized double-blind trial of placebo or n-3 PUFA supplementation (Lovaza 465 mg eicosapentaenoic acid (EPA) + 375 mg docosahexaenoic acid (DHA)) at "low" (1/day, 900 mg) or "high" (4/day, 3600 mg) dose in healthy individuals (N = 60; age 18-45; BMI 18-30; 43% female; 65% European-, 20% African-, 15% Asian-ancestry) before a low-dose endotoxin challenge (LPS 0.6 ng/kg intravenous bolus). The endotoxemia-induced temperature increase was significantly reduced with high-dose (p = 0.03) but not low-dose EPA + DHA compared to placebo. Although there was no statistically significant impact of EPA + DHA on individual inflammatory responses (tumor necrosis factor-α (TNF-α), IL-6, monocyte chemotactic protein (MCP-1), IL-1 receptor agonist (IL-1RA), IL-10, C-reactive protein (CRP), serum amyloid A (SAA)), there was a pattern of lower responses across all biomarkers with high-dose (nine of nine observed), but not low-dose EPA + DHA.. EPA + DHA at 3600 mg/day, but not 900 mg/day, reduced fever and had a pattern of attenuated LPS induction of plasma inflammatory markers during endotoxemia. Clinically and nutritionally relevant long-chain n-3 PUFA regimens may have specific, dose-dependent, anti-inflammatory actions.

Topics: Adolescent; Adult; Dietary Supplements; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Drug Combinations; Eicosapentaenoic Acid; Endotoxemia; Fatty Acids, Omega-3; Female; Fish Oils; Healthy Volunteers; Humans; Inflammation; Isoprostanes; Lipopolysaccharides; Lipoproteins; Male; Middle Aged; Young Adult

To examine n-3 polyunsaturated fatty acid (PUFA) incorporation into atherosclerotic plaques and the association with plaque inflammation and stability.. Patients awaiting carotid endarterectomy (n=121) were randomised to consume control capsules or n-3 PUFA ethyl ester capsules until surgery (median 21 days). The fatty acid compositions of plasma and carotid plaque phospholipids, plaque features, and expression of inflammatory genes were determined. The proportion of eicosapentaenoic acid (EPA) was higher (P<0.0001) in carotid plaque phospholipids in patients in the n-3 PUFA group. Plaques from patients in the n-3 PUFA group had fewer foam cells (P=0.0390). There were no other differences between plaques in the two groups with regard to histological characteristics or morphology. Plaque stability was not different between the two groups. However, the EPA content of plaque phospholipids was inversely associated with plaque instability (P=0.0209), plaque inflammation (P=0.0108), the number of T cells in the plaque (P=0.0097) and a summary score considering a range of plaque features (P=0.0425). Plaques from patients who received n-3 PUFAs had significantly lower levels of mRNA for matrix metalloproteinases (MMP)-7 (P=0.0055), -9 (P=0.0048) and -12 (P=0.0044) and for interleukin-6 (P=0.0395) and intercellular adhesion molecule 1 (P=0.0142).. Atherosclerotic plaques readily incorporate EPA. A higher plaque EPA content is associated with a reduced number of foam cells and T cells, less inflammation and increased stability.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Capsules; Carotid Artery Diseases; Chi-Square Distribution; Cytokines; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Eicosapentaenoic Acid; Endarterectomy, Carotid; England; Female; Foam Cells; Gene Expression Regulation; Humans; Inflammation; Inflammation Mediators; Male; Matrix Metalloproteinases; Middle Aged; Phospholipids; Preoperative Care; RNA, Messenger; Rupture, Spontaneous; T-Lymphocytes; Treatment Outcome

The objective of this study was to determine the effects of prescription omega-3 (n-3) fatty acid ethyl esters (Omacor®) on blood pressure, plasma lipids, and inflammatory marker concentrations in patients awaiting carotid endarterectomy. Patients awaiting carotid endarterectomy (n = 121) were randomised to Omacor® or olive oil as placebo (2 g/day) until surgery (median 21 days). Blood pressure, plasma lipids, and plasma inflammatory markers were determined. There were significant decreases in systolic and diastolic blood pressure and in plasma triglyceride, total cholesterol, low density lipoprotein-cholesterol, soluble vascular cellular adhesion molecule 1, and matrix metalloproteinase 2 concentrations, in both groups. The extent of triglyceride lowering was greater with Omacor® (25%) compared with placebo (9%). Soluble E-selectin concentration was significantly decreased in the Omacor® group but increased in the placebo group. At the end of the supplementation period there were no differences in blood pressure or in plasma lipid and inflammatory marker concentrations between the two groups. It is concluded that Omacor® given at 2 g/day for an average of 21 days to patients with advanced carotid atherosclerosis lowers triglycerides and soluble E-selectin concentrations, but has limited broad impact on the plasma lipid profile or on inflammatory markers. This may be because the duration of intervention was too short or the dose of n-3 fatty acids was too low.

Topics: Aged; Biomarkers; Blood Pressure; Carotid Artery Diseases; Cholesterol; Docosahexaenoic Acids; Drug Combinations; E-Selectin; Eicosapentaenoic Acid; Endarterectomy, Carotid; Esters; Fatty Acids, Omega-3; Female; Humans; Inflammation; Lipids; Lipoproteins, LDL; Male; Matrix Metalloproteinase 2; Triglycerides; Vascular Cell Adhesion Molecule-1

Topics: Administration, Oral; Capsules; Carotid Artery Diseases; Dietary Supplements; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Endarterectomy, Carotid; Foam Cells; Gene Expression Regulation; Humans; Inflammation; Inflammation Mediators; Matrix Metalloproteinases; Phospholipids; Preoperative Care; Rupture, Spontaneous; T-Lymphocytes; Treatment Outcome